DESCRIPTION: The specific aims of this project include: 1) to study proinflammatory cytokine secretory responses of primary oral epithelial cell cultures to C. albicans challenge, including production of IL-6 and IL-8 and determination of parasite factors associated with cytokine response; 2) to study mechanisms of host cell-C. albicans interactions which lead to proinflammatory cytokine responses, including necessity for direct contact and mannose-mediated signaling in eliciting IL-6 and IL-8 responses, as well as assessment of possible secondary cytokine-generated signals for IL-6 and IL-8 synthesis; and 3) to determine whether neutrophil anti-fungal activity can be regulated by interaction of C. albicans with oral epithelial cells, including activation of C. albicans phagocytosis and enhancement of fungicidal neutrophil activity in response to the proinflammatory cytokines secreted by epithelial cells challenged with C. albicans.